HUMAN BIOLOGY

CELL TO CELL COMMUNICATION - 1

Dr. Dinesh Kumar Department of Life Sciences International Medical University

Learning Objectives
At the end of this lecture you should be able: to know about cellular junctions to understand ligand-receptor concept to know about receptor linked channels and G-proteins

Cell Communication
Cells communicate with one another in complex ways to govern their own behavior for the benefit of the organism as a whole. Cell communications depend on extracellular signal molecules which are produced by cells to signal to their neighbors or to cells further away.

Cell communication - Example

Signal molecule

Distant Cell

How do cells communicate?

How do cells communicate?

The process must involve three stages.
In reception, a chemical signal binds to a cellular protein (receptor), typically at the cells surface. In transduction, binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway. In response, the transduced signal triggers a specific cellular activity.

Animal cell and plasma membrane

1. Membrane junctions
Usually there is a space between plasma membranes of adjacent cells, filled with extracellular fluid and provides pathway for substances to pass between cells. This space is called as a junction. Cells within a tissue are connected to each other by cell junctions or otherwise called as membrane junctions.

Membrane/cellular junctions
Desmosomes Tight junctions Gap junctions Adherens junctions

Desmosomes
Consist of a region between two adjacent cells separated by 20 nm.
Have a dense accumulation of protein at cytoplasmic surface of each membrane and in the space between the two membranes.

Protein fibers extend from cytoplasmic surface of desmosomes across the cell and are
Linked to other desmosomes on opposite side of the cell.

Desmosomes function to hold adjacent cells firmly together

Subject to considerable stretching Eg. Skin cells.

Desmosomes

Tight junctions
They are impermeable junctions Most epithelial cells are joined by tight junctions. A series of protein molecules in plasma membranes of adjacent cells fuse together. They prevent molecules passing through extracellular space between cells.

Eg: tight junctions between epithelial cells lining digestive tract Keep digestive enzymes and microorganisms in the intestine from seeping into bloodstream.

Tight junction

Gap junctions
Membrane junctions allow chemical messengers from one cell to another cell. Communicating junctions between adjacent cells. At gap junctions adjacent plasma membranes are very close & cells are connected by connexons composed of transmembrane proteins. Ions, simple sugars & small molecules pass through them. Present in electrically excitable tissues, such as heart & smooth muscle.

Gap junction

Adherens junctions
Adherens junctions provide strong mechanical attachments between adjacent cells. They hold:
cardiac muscle cells tightly together as the heart expands and contracts. epithelial cells together.

Adherens junctions are composed of the following proteins:

Cadherins are transmembrane proteins (shown in red) whose
extracellular segments bind to each other and whose intracellular segments bind to catenin

Catenin (yellow) which are connected to actin filaments

Adherens junction

Membrane junctions

Ligand-Receptor concept
Ligand: Signaling chemicals or first messengers
Any molecule or ion bound to specific sites on the surface of a protein. That bind specifically to membrane proteins or receptors. Chemical messengers: are various hormones, transmitters & other mediators.

Membrane receptors:
Group of integral proteins.

Receptors are the sensing elements in the system of chemical communications and coordinates the function of all different cells in the body. Protein binding site: region of a receptor protein to which a ligand binds.

Properties of a protein binding site

Chemical specificity Affinity Saturation Competition

CHEMICAL SPECIFICITY
Force of electrical attraction between oppositely charged regions on a protein and a ligand. Complementary shapes of ligand and protein binding site determine the chemical specificity of binding.

Affinity
Is the strength of ligand-protein binding.
High affinity Intermediate affinity Low affinity

Affinity & chemical specificity properties of binding sites.

are

two

distinct,

Chemical specificity depends on shape of binding site Affinity depends on strength between protein & ligand.

Affinity
Three binding sites with the same chemical specificity for a ligand but different affinities.

Saturation
The fraction of total binding sites occupied at any given time. When all binding sites occupied,
The population of binding sites is 100% saturated.

When half the available sites are occupied,

The system is 50% saturated & so on.

Competition
More than one type of ligand can bind to certain binding sites. Competition occurs between ligands for the same binding site. Presence of multiple ligands, to bind the same binding site affects the % of binding sites occupied by any one ligand.

Competition

Role of membrane receptors

Some function in contact signaling & others in chemical signaling.
Contact signaling- the actual touching of cells
By which cells recognize one another. Important for normal development & immunity. Some bacteria & infectious agents use contact signaling To identify its target tissues or organs.

Most plasma membrane receptors are involved in chemical signaling

Signaling chemicals or ligands bind specifically to plasma membrane receptors Different cells respond differently to the same ligand. Eg: Acetylcholine stimulates skeletal muscle cells to contract, but inhibits heart muscle.

Modes of communication
There are four basic mechanisms for cellular communication: 1. 2. 3. 4. Direct contact Paracrine signaling Endocrine signaling Synaptic signaling

Direct contact
In direct contact the molecules on the surface of one cell are recognized by receptors on the adjacent cell

Paracrine signaling
Here the signal released from a cell has an effect on neighboring cells

Endocrine signaling
In endocrine signaling the hormones released from a cell affect other cells throughout the body.

Synaptic signaling
In this type the nerve cells release the signal (neurotransmitter) which binds to receptors on nearby cells.

Types of receptors
PLASMA-MEMBRANE RECEPTORS

For lipidinsoluble messengers

Receptors that function as ion channels. Receptors that function as enzymes. Receptors that activate G proteins

Which in turn act upon effector proteins either ion channels or enzymes in the plasma membrane.

Receptors Ion channels

Protein that acts as the receptor itself constitutes an ion channel Activation of the receptor by a first messenger causes the channel to open (voltage-gated channels and ligand-gated channels) Highly selective for transport of ions or molecule Results in an increase in net diffusion across the plasma membrane of the ion or ions specific to the channel. They respond to changes in membrane potential by opening or closing the channel (voltage-gated channels)

Receptors Ion channels

Such a change in ion diffusion changes membrane potential & causes electrical signaling. This electric signal is the essential event in cells response to the messenger. Common in excitable tissues (neural & muscle)

Receptors Ion channels

Gating of protein channels

Chemical (ligand) gating

Some protein channel gates are opened by binding of a chemical substance (a ligand) with protein. This causes a conformational or chemical change in the protein molecule. that opens or closes the gate. This is called chemical gating or ligand gating.

Enzyme linked receptors

Many PM receptors possess intrinsic enzyme activity & all are protein kinases. They all involve in activation of cytoplasmic proteins by phosphorylation. The binding of a specific messenger to the receptor changes Conformation of the receptors enzymatic portion, on cytoplasmic side of PM & activates receptor. This results in autophosphorylation (addition of phosphate group) of the receptor and phosphorylates its own tyrosine groups. The newly created phosphotyrosines on cytoplasmic portion serve as docking sites for cytoplasmic proteins.

Enzyme linked receptors

The bound docking proteins then bind other proteins Leads to a cascade of signaling pathways within the cell. Large number of kinases mediate these phosphorylations.

At the end of these sequences the ultimate phosphorylation of key proteins underlies The cells response to the original first messenger.

Receptors with G proteins

These are transmembrane receptors coupled to intracellular effector systems via a G-protein

A protein bound to this receptor on inside surface (cytosolic) of the PM - called G proteins.
Their characteristic structure comprises:

Seven transmembrane spanning helices With an extra-cellular N-terminal domain & An intra-cellular C-terminal domain.

Receptors with G proteins

Receptors with G proteins

G-proteins Whose function is to recognize activated GPCRs & Pass the message to effector systems (second messengers) that generate a cellular response. G-proteins consist of 3 subunits: , & . Guanosine triphosphate (GTP) binds to the subunit has enzymic activity, catalyzing the conversion of GTP to GDP.

Receptors with G proteins

The and subunits remain together as a complex. All 3 subunits (, & ) are anchored to the plasma membrane The binding of a first messenger to the receptor changes the conformation of the receptor. This change causes one of the three subunits of the G protein to link up with another PM protein either an ion channel or an enzyme.

Receptors with G proteins

The G protein may cause the ion channel to open, with resulting generation of electric signals. G protein may activate or inhibit the membrane enzyme with which it interacts & generation of second messengers inside the cell.

Receptors with G proteins

G protein coupled receptors (GPCRs) - exert their effect indirectly through a G protein Acts as or relay to activate (or inactivate) a membrane-bound enzyme or ion channel. G-proteins are freely diffusible in the plane of the membrane, A single pool of G-protein in a cell can interact with several different receptors & effectors.

References
1.Rang & Dales Pharmacology, 6th edition chapter 3 2. Molecular Biology of Cell, 5th edition , Alberts, Johnson, Lews, Raff, Roberts, Walter